|
|
||||||||
ORIGINAL RESEARCH COMMUNICATION |
1 From the Division of Community Health Sciences, St George's, University of London, London, United Kingdom (CGO, PHW, and DGC); the Department of Social Medicine, University of Bristol, Bristol, United Kingdom (RMM and GD-S); and the Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, MA (MWG)
2 Supported by the British Heart Foundation (project grant no. PG/04/072 to CGO) and by the Wellcome Trust (reference GR063779MA to RMM).
3 Reprints not available. Address correspondence to CG Owen, Division of Community Health Sciences, St George's, University of London, Cranmer Terrace, London SW17 ORE, United Kingdom. E-mail: c.owen{at}sgul.ac.uk.
| ABSTRACT |
|---|
|
|
|---|
Objective: The objective was to examine whether initial breastfeeding is related to lower mean body mass index (BMI; in kg/m2) throughout life.
Design: The study was a systematic review of published studies investigating the association between infant feeding and a measure of obesity or adiposity in later life, which was supplemented with data from unpublished sources. Analyses were based on the mean differences in BMI between those subjects who were initially breastfed and those who were formula-fed (expressed as breastfed minus bottle-fed), which were pooled by using fixed-effects models throughout.
Results: From 70 eligible studies, 36 mean differences in BMI (from 355 301 subjects) between those breastfed and those formula-fed (reported as exclusive feeding in 20 studies) were obtained. Breastfeeding was associated with a slightly lower mean BMI than was formula feeding (0.04; 95% CI: 0.05, 0.02). The mean difference in BMIs appeared larger in 15 small studies of <1000 subjects (0.19; 95% CI: 0.31, 0.08) and smaller in larger studies of
1000 subjects (0.03; 95% CI: 0.05, 0.02). An Egger test was statistically significant (P = 0.002). Adjustment for socioeconomic status, maternal smoking in pregnancy, and maternal BMI in 11 studies abolished the effect (0.10; 95% CI: 0.14, 0.06 before adjustment; 0.01; 95% CI: 0.05, 0.03 after adjustment).
Conclusions: Mean BMI is lower among breastfed subjects. However, the difference is small and is likely to be strongly influenced by publication bias and confounding factors. Promotion of breastfeeding, although important for other reasons, is not likely to reduce mean BMI.
Key Words: Infant feeding body mass index systematic review
| INTRODUCTION |
|---|
|
|
|---|
Although earlier studies focused mainly on whether breastfeeding reduces the prevalence of obesity, it is also important to establish whether it reduces average levels of adiposity, which is most commonly measured with the use of body mass index (BMI; in kg/m2). This is important because the risks of cardiovascular disease and type 2 diabetes associated with obesity are graded and are increased at the mean BMIs occurring in many adult populations, not only at exceptionally high BMIs (9, 10).
Few studies have published data on the relation of infant feeding to mean BMI; as is the case for obesity prevalence, the results have been conflicting, showing both protective (11) and null (5) effects. We therefore reviewed the published literature and obtained data from previously unpublished sources to quantify the association between infant feeding and mean BMIs in later life. To standardize the presentation of results and minimize the extent of publication and reporting bias, we have systematically requested a series of estimates of mean BMIs from the authors of individual studies. The request for data also allowed for exploration of the effect of adjustment for confounding factors identified in an earlier review as important (6).
| METHODS |
|---|
|
|
|---|
Unpublished data sources
Unpublished data were obtained from another national cohort (14), a national survey (15), other cohort and cross-sectional studies with data on early life exposures and measures of adiposity or obesity in later life (16-23). These represent 10 studies (with 28 985 subjects) in addition to the 60 studies previously identified, for a total of 70 studies with 414 750 subjects.
Outcome measurement
Although studies in infants and young children used measures of body size based on weight-for-length (24, 25) or weight (24-26), or both, mean differences in BMI were sought and were considered an appropriate measure of weight-for-height in this age group (
3 mo old). Mean differences were extracted from the published literature where available. There was considerable variation in the presentation of results, with most studies reporting odds ratios (ORs) for obesity (using a variety of definitions) in preference to reporting mean differences in BMI. Mean BMI differences between breastfed and formula-fed infants were reported from only 10 (14%) of the 70 studies (5, 11, 12, 23, 27-32). To obtain further data and to standardize the format of the results, the reviewers devised a data request form. Attempts were made to obtain additional data from authors of all of the eligible studies. However, further information could not be obtained for 8 historical studies (published in the 1970s and 1980s) because contact addresses of study authors could not be found (33-40). None of these historic studies published mean differences in BMI; 3 published ORs (35, 38, 39) that have been included in a recent review (6). Requests for data were made to corresponding authors or Principal Investigators (or both) of 62 remaining studies, and individual data from 2 national studies were requested from the UK Data Archive. Hence, requests were made to 64 of the 70 eligible studies (91%). Where outcomes were measured at various ages throughout the lifecourse, the oldest age at ascertainment of BMI was included in the meta-analysis.
Assessment of infant feeding exposure
Authors were asked whether initial infant feeding status was ascertained from records or maternal recall at the time of infant feeding or from recall some years after birth. Information was extracted from the published literature when it was not possible to obtain data form the authors directly. Authors were asked to report the median duration of exclusive breastfeeding, exclusive bottle feeding, or mixed feeding [defined as breastfeeding and bottle (ie, formula) feeding]; the number of subjects; and the mean (±SEM) BMI in each feeding group, for males and females separately. The World Health Organization defines exclusive breastfeeding as breastfeeding while giving no other food or liquidnot even waterfor the first 4 mo (and, if possible, for the first 6 mo) of life (41). Whereas we asked for BMI data for exclusive feeders, few studies report this definition. Hence, the exclusiveness of infant feeding is based on the classification given in individual study reports or where applicable reported directly by the author (Table 1
). Bottle feeders were assumed to have been fed formula milk, not human milk, throughout.
|
age: < 16 y) were based on the SES of the head-of-household parent; in adults, they were based or the subject's own SES. Authors were asked to specify whether SES was based on occupation, salary, or education or on all 3 variables. Data on the type of formula feed, year of birth, mean age, and minimum and maximum age of participants were also requested. Mean differences in BMI between those breast and bottle-fed (defined as breastfed bottle-fed) were sought (1) without adjustment (to verify the reported means), (2) with adjustment for age only, (3) with adjustment for age and each of either SES, maternal BMI, or maternal smoking in pregnancy, or (4) with adjustment for age and SES, maternal BMI, and maternal smoking in pregnancy combined. Authors were invited to provide an anonymized data set if they were unable to carry out the analyses requested.
Statistical analysis
To carry out the meta-analyses, we used the mean difference in BMI between those initially breastfed and those formula-fed and the SE of the difference from each study, with the adjustments listed above. Separate analyses for males and females and for the sexes combined (also adjusted for sex) were conducted. Fixed effect models are reported throughout, because these reflect only the random error within each study and are less affected by publication bias (whereas small studies tend to publish larger estimates). Heterogeneity of the mean differences in BMI between studies was examined by using chi-square tests. Small-study bias was assessed by using funnel plots, Begg tests, and Egger tests (57-59). Meta-regression, which offers a conservative test of the effect of certain exposures on outcome (assessed at the study level), was used to examine the influence of the following factors (defined a priori) by using a test for trend: study size (<500, 5002500, or > 2500 breastfed and formula-fed subjects), quintiles of age at outcome measurement (infants and young children, child aged < 5 y, children aged
58 y, older children and adolescents aged > 816 y, and adults > 16 y), year of birth (including whether born before or after 1980). The effect of the method of ascertainment of infant feeding status (whether contemporary or recalled over a period of
3 y) was also examined. Meta-regression and sensitivity analyses (which excluded studies with particular characteristics) were also used to examine the influence of exclusive feeding, duration of breastfeeding (in those ever breastfed and those exclusively breastfed). Meta-regression tests were adjusted for study size.
To establish the likelihood of reporting bias, we compared pooled mean differences from studies that reported (either quantitatively or narratively; in the latter case, additional data obtained from the authors were used) on the direction of the association between infant feeding and any measure of adiposity found in the published literature with differences from those that did not publish on the association at all or those that published a mean difference in BMI (or both) and from those that did not publish a mean difference but provided an estimate in response to the request for data. In addition, we examined the effect of including data from 4 studies that did not provide data but when estimates could be derived from the published literature. Meta-regressions to examine reporting bias were not adjusted for study size.
| RESULTS |
|---|
|
|
|---|
58 y), 9 in older children and adolescents (aged > 816 y), and 11 in adults aged > 16 y (Table 1
difference: 0.04; 95% CI: 0.05, 0.02; Figure 2
age: 34 y); exclusion of these studies increased the mean difference in BMI between those who were breastfed and those who were formula-fed (0.09; 95% CI: 0.11, 0.06).
|
|
|
|
Influence of age at outcome and sex
The difference in mean BMI between infant feeding groups varied somewhat with age at outcome measurement. A mean difference of 0.01 (95% CI: 0.03, 0.01) in infants and children aged < 5 y, of 0.05 (95% CI: 0.08, 0.02) in children aged 59 y, of 0.19 (95% CI: 0.25, 0.13) in older children and adolescents, and of 0.11 (95% CI: 0.17, 0.04) in adults was observed. However, neither a test for overall age differences (P = 0.28) nor a test for trend across age groups (treating mean age as a continuous variable) were statistically significant (P = 0.32). Year of birth was unrelated to mean differences in BMI (P = 0.32). In 32 studies that provided data by sex, the mean difference did not differ significantly between males (0.06; 95% CI: 0.09, 0.03) and females (0.09; 95% CI: 0.13, 0.06).
Influence of potential confounding factors
In 28 studies, it was possible to examine the effect of adjustment for SES (based on parental status in studies of infants and children or on individual status in studies of adults; Table 1
and Table 3
). The age-adjusted difference in mean BMI was similar before and after adjustment for SES; considerable heterogeneity remained between study estimates (Table 3
). Similarly, adjustment for maternal smoking in pregnancy (10 studies) had little effect on the mean difference observed (Table 3
). In 18 studies, it was possible to examine the effect of adjustment for maternal BMI [parental BMI was used in one study (5)]. The age-adjusted mean difference was reduced from 0.11 to 0.05 after adjustment for maternal BMI (Table 3
). A test for heterogeneity was of borderline statistical significance (P < 0.001 before adjustment; P = 0.079 after adjustment). The effect of combined adjustment for SES, maternal BMI, and maternal smoking during pregnancy could be examined in the 11 studies that provided data. The age-adjusted mean difference (0.10; 95% CI: 0.14, 0.06) was effectively abolished after adjustment for these 3 factors (adjusted mean difference: 0.01; 95% CI: 0.05, 0.03). In 9 of the 11 individual studies, the pattern was similara negative effect before adjustment, which was either reduced in magnitude or became positive after adjustment for the 3 factors. A further study showed no change in mean BMI after adjustment, and another showed a slight increase after adjustment. Adjustment for these 3 factors appeared to explain some of the heterogeneity between estimates (P < 0.001 with adjustment for age; P = 0.022 with adjustment for age and the other 3 factors).
|
3 y after birth (43, 44). The difference in mean BMI appeared somewhat smaller between 20 studies in which initial feeding groups were definitely exclusive (0.06; 95% CI: 0.09, 0.04) and 12 studies that did not report whether feeding was exclusive (0.13; 95% CI: 0.18, 0.08). However, this difference was not statistically significant (P = 0.45).
Prolonged breastfeeding appeared to show a slightly greater protective effect on mean levels of adiposity than did breastfeeding for a shorter time. In 18 studies that reported on exclusive breastfeeding, the difference between the protective effect of breastfeeding and that of formula feeding was shown to be greatest in subjects who were breastfed for the longest time: in the 3 studies that reported exclusive breastfeeding for
8 mo (23, 25, 28), the mean difference was 0.39 (95% CI: 0.51, 0.26), whereas the mean difference for both tertiles of shorter breastfeeding was 0.05. In a meta-regression, each additional month of exclusive breastfeeding was associated with a decrease of 0.04 in mean BMI (95% CI: 0.06, 0.01; P = 0.008). The protective effect of exclusive breastfeeding for
8 mo was abolished in 2 studies (23, 28) after adjustment for SES, maternal BMI, and maternal smoking (from 0.4 to 0.02 after adjustment). Similar but weaker findings were observed when the duration of feeding was considered in subjects exclusively and subjects nonexclusively breastfed (data not presented).
| DISCUSSION |
|---|
|
|
|---|
In our recent review of 28 published studies, in which we examined the influence of initial feeding on the odds of obesity in later life (6), the overall OR of obesity (mostly based on the 95th or 97th percentile of the BMI distribution) was 0.87 (95% CI: 0.85, 0.89). Assuming a normal distribution of BMI and a conservative estimate of 2 SD in BMIs (6, 60), this OR would be consistent with an overall mean difference in BMIs between infant feeding groups of 0.15 (95% CI: 0.18, 0.13). The higher mean difference estimated from the previous reviewwhich was based entirely on published literature (6)than the present estimated difference (0.08; 95% CI: 0.10, 0.05; derived from both published and unpublished sources) may be explained by several factors. One potential explanation is publication bias. There was some evidence of small-study bias in the current review when we stratified the pooled analyses by study size and by using the Egger test (61), which is a more sensitive test for small-study bias than is the Begg test. These observations, combined with our sensitivity analyses of differences between published and unpublished estimates, suggest that publication bias is a potential concern in interpreting the published literature. An alternative explanation for the presence of stronger associations in small studies, ie, more precise exposure measurement, seems unlikely here; methods of ascertaining infant feeding did not differ systematically between smaller and larger studies and had little or no relation to outcome in a sensitivity analysis. It is also possible that breastfeeding is associated with a lower prevalence of obesity, but that it has no relation with mean BMI. Such a situation could occur if breastfeeding were associated not only with a lower prevalence of obesity but also with a lower prevalence of underweight, which would leave the mean BMI unchanged, as has been suggested by other investigators (32). Further examination of the association between infant feeding and underweight in later life is needed.
Although obtaining data directly from study authors allowed for standardization of data presentation by permitting examination of the influence of exposures such as prolonged breastfeeding, there was heterogeneity in mean differences in BMI across studies. This may well reflect the fact that participating studies were all observational and that variable degrees of confounding were present. Analysis based on 11 studies in which we able to obtain adjustment for 3 major confounders reduced the heterogeneity between study estimates. Adjustment for measures of size at birth may be important, especially because higher birth weight might be associated with formula feeding and with a higher BMI in later life (45, 62). However, a recent systematic review of a small number of studies with adjustment for size at birth failed to find any substantive effect of that variable on the magnitude of the associations between breastfeeding and the prevalence of obesity (6).
The null effect observed after simultaneous adjustment for important confounders in 11 studies is of considerable interest and suggests that apparent protective effects of breastfeeding on adiposity may be explained by confounding. This finding is consistent with our earlier meta-analysis of ORs, which found that the protective effect of infant feeding on obesity was reduced from an OR of 0.86 to an OR of 0.93 in 6 studies that included adjustment for SES, parental BMI, and maternal smoking (6). However, to confirm this finding, further data are needed from studies that use simultaneous adjustment for important confounders. Randomized trials or studies in populations without social gradients in infant feeding (such as those from the developing world) may also be useful for confirming that observed effects are explained by residual confounding. However, experimental studies are generally impractical in this context, except in specific circumstances of preterm birth or randomized controlled trials of breastfeeding promotion (63, 64).
Although the overall and adjusted estimates of mean differences in BMI between breastfeeders and bottle feeders were modest, there was some evidence that prolonged breastfeeding was associated with a larger difference in BMI. It is possible that prolonged breastfeeding confers greater protection (and provides evidence of a dose-response relation), but the evidence from this review was weak, and further examination of this issue is needed. Some evidence indicates that the relation of breastfeeding to mean BMI differed with age and is stronger in adolescents. However, if the effect in adolescence is real, the relatively small difference in BMIs observed in adults (in whom the consequences of obesity are of greatest public health significance) implies that the long-term importance of breastfeeding is limited.
Although a protective effect of breastfeeding on levels of adiposity in later life is biologically plausible (3, 65, 66), our results suggest that, overall, breastfeeding is associated with at most a small effect on BMI in adolescence and adult life. Even if a protective effect of breastfeeding on BMI at the upper 95% confidence limit (ie, 0.2) in these age groups were observed, that would result in a reduction of
1% in the incidence of CHD and type 2 diabetes, according to earlier observational data that suggested that a decrease in BMI (from 21.9 to 20.0) was associated with a 10% reduction in coronary events and diabetes (9). Encouraging breastfeeding for the purpose of reducing mean BMIs cannot therefore be advocated on the basis of this review. However, it remains possible that breastfeeding provides some protection against obesity (6). In addition, breastfeeding has numerous other health benefits, including improved neural and psychosocial development (67, 68) and has the potential to protect against allergic disease (69) and lower blood cholesterol levels in later life (16).
| ACKNOWLEDGMENTS |
|---|
All authors contributed substantially to the conception and design of the study. RMM carried out the literature search, CGO sent the data request, coordinated the search for unpublished data sources, carried out statistical analysis, and drafted the manuscript. The manuscript was critiqued by all authors for intellectual content; CGO acts as guarantor (who accepts full responsibility for the integrity of the work as a whole). All authors had access to the data and approved the final version of the manuscript. None of the authors had any personal or financial conflicts of interest.
| REFERENCES |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
M. S Kramer Reply to AE Buyken et al Am. J. Clinical Nutrition, June 1, 2008; 87(6): 1965 - 1966. [Full Text] [PDF] |
||||
![]() |
E. Mok, C. Multon, L. Piguel, E. Barroso, V. Goua, P. Christin, M.-J. Perez, and R. Hankard Decreased Full Breastfeeding, Altered Practices, Perceptions, and Infant Weight Change of Prepregnant Obese Women: A Need for Extra Support Pediatrics, May 1, 2008; 121(5): e1319 - e1324. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. G. Woo, L. M. Dolan, A. L. Morrow, S. R. Geraghty, and E. Goodman Breastfeeding Helps Explain Racial and Socioeconomic Status Disparities in Adolescent Adiposity Pediatrics, March 1, 2008; 121(3): e458 - e465. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. S Kramer, L. Matush, I. Vanilovich, R. W Platt, N. Bogdanovich, Z. Sevkovskaya, I. Dzikovich, G. Shishko, J.-P. Collet, R. M Martin, et al. Effects of prolonged and exclusive breastfeeding on child height, weight, adiposity, and blood pressure at age 6.5 y: evidence from a large randomized trial Am. J. Clinical Nutrition, December 1, 2007; 86(6): 1717 - 1721. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. M. Davis, B. Gance-Cleveland, S. Hassink, R. Johnson, G. Paradis, and K. Resnicow Recommendations for Prevention of Childhood Obesity Pediatrics, December 1, 2007; 120(Supplement_4): S229 - S253. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. F Butte, G. Cai, S. A Cole, T. A Wilson, J. O Fisher, I. F Zakeri, K. J Ellis, and A. G Comuzzie Metabolic and behavioral predictors of weight gain in Hispanic children: the Viva la Familia Study Am. J. Clinical Nutrition, June 1, 2007; 85(6): 1478 - 1485. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. M Toschke, R. M Martin, R. von Kries, J. Wells, G. Davey Smith, and A. R Ness Infant feeding method and obesity: body mass index and dual-energy X-ray absorptiometry measurements at 9-10 y of age from the Avon Longitudinal Study of Parents and Children (ALSPAC) Am. J. Clinical Nutrition, June 1, 2007; 85(6): 1578 - 1585. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. R. Rudnicka, C. G. Owen, and D. P. Strachan The Effect of Breastfeeding on Cardiorespiratory Risk Factors in Adult Life Pediatrics, May 1, 2007; 119(5): e1107 - e1115. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Scholtens, U. Gehring, B. Brunekreef, H. A. Smit, J. C. de Jongste, M. Kerkhof, J. Gerritsen, and A. H. Wijga Breastfeeding, Weight Gain in Infancy, and Overweight at Seven Years of Age: The Prevention and Incidence of Asthma and Mite Allergy Birth Cohort Study Am. J. Epidemiol., April 15, 2007; 165(8): 919 - 926. [Abstract] [Full Text] [PDF] |
||||
![]() |
T. Byers and R. L. Sedjo Public Health Response to the Obesity Epidemic: Too Soon or Too Late? J. Nutr., February 1, 2007; 137(2): 488 - 492. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Schack-Nielsen and K. F. Michaelsen Advances in Our Understanding of the Biology of Human Milk and Its Effects on the Offspring J. Nutr., February 1, 2007; 137(2): 503S - 510S. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. M. Taveras, S. L. Rifas-Shiman, K. S. Scanlon, L. M. Grummer-Strawn, B. Sherry, and M. W. Gillman To What Extent Is the Protective Effect of Breastfeeding on Future Overweight Explained by Decreased Maternal Feeding Restriction? Pediatrics, December 1, 2006; 118(6): 2341 - 2348. [Abstract] [Full Text] [PDF] |
||||
![]() |
C. G Owen, R. M Martin, P. H Whincup, G. D. Smith, and D. G Cook Does breastfeeding influence risk of type 2 diabetes in later life? A quantitative analysis of published evidence. Am. J. Clinical Nutrition, November 1, 2006; 84(5): 1043 - 1054. [Abstract] [Full Text] [PDF] |
||||
![]() |
D. Fisher, J. Baird, L. Payne, P. Lucas, J. Kleijnen, H. Roberts, and C. Law Are infant size and growth related to burden of disease in adulthood? A systematic review of literature Int. J. Epidemiol., October 1, 2006; 35(5): 1196 - 1210. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. F Butte, G. Cai, S. A Cole, and A. G Comuzzie Viva la Familia Study: genetic and environmental contributions to childhood obesity and its comorbidities in the Hispanic population. Am. J. Clinical Nutrition, September 1, 2006; 84(3): 646 - 654. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. S. HAWKINS and C. LAW Treatment and prevention of obesity--are there critical periods for intervention? Int. J. Epidemiol., August 1, 2006; 35(4): 1101 - 1101. [Full Text] |